Parathyroid hormone, or PTH, is a protein product of mammalian parathyroid glands that elicits various biological effects of clinical interest. Of considerable current interest is the role of PTH as a mediator of the physiologically normal, bone remodelling process. In this regard, PTH acts by stimulating bone tissue to modulate skeletal calcium deposit, and thus can mediate an increase in bone mass. It has been suggested that the administration of PTH, or agonistic analogues thereof, would be useful therapeutically to treat and/or prevent bone-related disorders, such as osteoporosis. It has also been revealed that PTH is a vasoactive protein, and exerts a vasorelaxant effect on the cardiovascular system, and may be useful in controlling systemic blood pressure (see for example the article by Tenner et al in Vascular Neuroeffector Mechanisms, 4th International Symposium, Raven Press, 1983, pp289-293; and see the review by Mok et al, Endocrine Reviews, 1989, 10(4):420).
To further the development of PTH as a bone therapeutic, it would be desirable to reduce its cardiovascular action, particularly so that repeated administration during treatment, for example of an osteoporotic patient, does not contribute to an altered cardiovascular state. Accordingly, it is a general object of the present invention to provide novel variants of parathyroid hormone that exhibit bone stimulating activity and reduced vasoactivity.
It is another object of the present invention to provide variants of parathyroid hormone having substantial bone stimulating activity and reduced vasoactivity, which are amenable to production by recombinant DNA technology.
It is also an object of the present invention to provide a pharmaceutically useful composition containing a novel parathyroid hormone variant that exhibits bone stimulating activity and reduced vasoactivity.
It is another object of the present invention to provide a method for treating patients afflicted with an osteopenic condition, such as osteoporosis.